Catheter systems

ABSTRACT

Catheter systems include direction-sensitive, multi-polar tip electrode assemblies for electroporation-mediated therapy, electroporation-induced primary necrosis therapy and electric field-induced apoptosis therapy, including configurations for producing narrow, linear lesions as well as distributed, wide area lesions. A monitoring system for electroporation therapy includes a mechanism for delivering electrochromic dyes to a tissue site as well as a fiber optic arrangement to optically monitor the progress of the therapy as well as to confirm success post-therapy. A fiber optic temperature sensing electrode catheter includes a tip electrode having a cavity whose inner surface is impregnated or coated with thermochromic/thermotropic material that changes color with changes in temperature. An optic fiber/detector arrangement monitors the thermochromic or thermotropic materials, acquiring a light signal and generating an output signal indicative of the spectrum of the light signal. An analyzer determines an electrode temperature based on the detector output and predetermined spectrum versus temperature calibration data.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.15/931,240, filed 13 May 2020 (the '240 application), now pending, whichis a continuation of U.S. application Ser. No. 15/064,664, filed 9 Mar.2016 (the '664 application), now U.S. Pat. No. 10,688,300, which is acontinuation of U.S. application Ser. No. 12/874,788, filed 2 Sep. 2010(the '788 application), now U.S. Pat. No. 9,289,606. The '240application, the '664 application and the '788 application are allhereby incorporated by reference as though fully set forth herein.

BACKGROUND OF THE INVENTION a. Field of the Invention

The instant invention relates generally to catheter systems.

b. Background Art

It is generally known that ablation therapy may be used to treat variousconditions afflicting the human anatomy. One such condition thatablation therapy finds a particular application is in the treatment ofatrial arrhythmias, for example. When tissue is ablated, or at leastsubjected to ablative energy generated by an ablation generator anddelivered by an ablation catheter, lesions form in the tissue.Electrodes mounted on or in ablation catheters are used to create tissuenecrosis in cardiac tissue to correct conditions such as atrialarrhythmia (including, but not limited to, ectopic atrial tachycardia,atrial fibrillation, and atrial flutter). Arrhythmia (i.e., irregularheart rhythm) can create a variety of dangerous conditions includingloss of synchronous atrioventricular contractions and stasis of bloodflow which can lead to a variety of ailments and even death. It isbelieved that the primary cause of atrial arrhythmia is stray electricalsignals within the left or right atrium of the heart. The ablationcatheter imparts ablative energy (e.g., radiofrequency energy,cryoablation, lasers, chemicals, high-intensity focused ultrasound,etc.) to cardiac tissue to create a lesion in the cardiac tissue. Thislesion disrupts undesirable electrical pathways and thereby limits orprevents stray electrical signals that lead to arrhythmias.

One candidate for use in therapy of cardiac arrhythmias iselectroporation. Electroporation therapy involves electric-field inducedpore formation on the cell membrane. The electric field may be inducedby applying a direct current (DC) signal delivered as a relatively shortduration pulse which may last, for instance, from a nanosecond toseveral milliseconds. Such a pulse may be repeated to form a pulsetrain. When such an electric field is applied to tissue in an in vivosetting, the cells in the tissue are subjected to trans-membranepotential, which essentially opens up the pores on the cell wall, hencethe term electroporation. Electroporation may be reversible (i.e., thetemporally-opened pores will reseal) or irreversible (i.e., the poreswill remain open). For example, in the field of gene therapy, reversibleelectroporation (i.e., temporarily open pores) are used to transfecthigh molecular weight therapeutic vectors into the cells. In othertherapeutic applications, a suitably configured pulse train alone may beused to cause cell destruction, for instance by causing irreversibleelectroporation.

Generally, for use in electrophysiological (EP) applications, thesuccess of electroporation therapy cannot be assessed instantaneously,such as in RF ablation. Instead, a clinician may have to wait a week ormore after delivering the therapy to clinically detect any therapeuticeffects. In the use of electroporation in cancer treatments, where thetherapeutic objective is to arrest tumor growth as well as to kill thetumor cell, confirmation of the therapeutic success based on theresolution of the tumor over a prolonged duration is common. However,such delayed therapeutic confirmation poses a severe limitation in usingelectroporation therapy in EP applications.

As further background for the case of cardiac ablation, physicianscustomarily use a three-step process: (1) performing diagnosticprocedures to identify the heart sites responsible for the arrhythmias;(2) delivering therapy, such as ablation, to the identified sites, basedon the results of the diagnostic procedure; and (3) monitoring theprogress of the therapy during delivery as well as afterwards to confirmits success (e.g., such as reduction of electrogram and restoration ofsinus rhythm). For electroporation to be adopted as a therapeutic step,for instance to be used in step number two above, a procedure to monitorand confirm the progress and ultimate success of the electroporationtherapy is needed. In addition, another feature of known electroporationapparatus is that they are characterized by electrode assemblies thatproduce an omni-directional electric field, which may undesirably affectnon-target tissue. It would be desirable to provide an apparatus withgreater selectivity with respect to what tissue is to be affected by thetherapy.

In addition, it is also known to use radio frequency (RF) energy forablation purposes in certain therapeutic applications. RF ablation istypically accomplished by transmission of RF energy using an electrodeassembly to ablate tissue at a target site. Because RF ablation maygenerate significant heat, which if not controlled can result inundesired or excessive tissue damage, such as steam pop, tissuecharring, and the like, it is common to include a mechanism to irrigatethe target area with biocompatible fluids, such as a saline solution.Another known mechanism to control heat is to provide an ablationgenerator with certain feedback control features, such as a temperaturereadout of the electrode temperature. To provide for such feedback tothe physician/clinician during the procedure, conventional RF ablationgenerators are typically configured for connection to a temperaturesensor, such as a thermocouple or thermistor, that is located within theablation electrode.

However, the use of either thermocouples or thermistors has spatiallimitations in terms of its placement in the electrode. A commonconventional irrigated ablation catheter design involves the use of adistal irrigation passageway in combination with an electrode-disposedthermal sensor. The distal irrigation passageway may be thermallyinsulated and is typically located on the center axis of the electrodeassembly. Because the distal irrigation passageway is located on thecenter axis, the thermal sensor must be moved away from the center axialposition. This off-center positioning of the thermal sensor is less thanideal since it could affect the temperature measurement. For example,consider the situation where the catheter electrode is in a parallelcontact orientation. The temperature reading will depend on which sideof the electrode is contacting the tissue, since it is on the contactside of the electrode where the significant heat will be generated(i.e., with the sensor being either closer to the contact-side for ahigher temperature reading or farther away from the contact-side for alower temperature reading). Moreover, typical thermocouples and/orthermistors are connected to external circuitry by way of wireconductors. Accordingly, these conventional arrangements are susceptibleto radio-frequency interference (RFI) and/or electromagneticinterference (EMI) by virtue of at least these connecting wires.

Electroporation therapy generally does not appreciably increase thetemperature of the tissue as in RF ablation to give rise to thermallymediated coagulum necrosis. Hence the use of thermal sensors to monitorthe creation of tissue necrosis from electroporation is generallyredundant. Moreover, duration of electric pulses used to cause tissuenecrosis by electroporation is much shorter than the time constants ofthe thermal sensors generally used in RF ablation applications.Therefore, a new way to monitor the efficacy of creating tissue necrosisdue to electroporation is needed.

There is therefore a need for catheter systems that minimize oreliminate one or more of the problems as set forth above.

BRIEF SUMMARY OF THE INVENTION

One advantage of the methods and apparatus described, depicted andclaimed herein relates to, in direction-sensitive electrode assemblyembodiments for electroporation therapy, an increased selectivity inwhat tissue is subjected to the electroporation therapy. Anotheradvantage of the methods and apparatus described, depicted and claimedherein relates to, in optical-based tissue sensing embodiments forelectroporation therapy, an improved procedure for monitoring both theprogress as well as the ultimate success of the therapy. A still furtheradvantage of the methods and apparatus described, depicted and claimedherein relates to, in fiber optic temperature sensing embodiments, animproved accuracy in electrode temperature measurement by avoidingerrors that would otherwise arise due to thermal sensor locationeccentricity (as described in the Background) as well as providingimmunity to RFI and EMI.

In a first aspect, this disclosure is directed to an electroporationtherapy system that comprises a device (e.g., a catheter) havingproximal and distal ends, an electrode assembly, a detector and anelectroporation generator. The electrode assembly includes a pluralityof electrically isolated electrode elements disposed at the distal endof the device. The detector is coupled to the plural electrode elementsand is configured to identify which elements have a conductioncharacteristic indicative of contact with tissue that is to be subjectedto the electroporation therapy. In an embodiment, the system may furtherinclude a tissue sensing circuit configured to determine a tissueproperty (as sensed through an electrode element or pair thereof) inorder to determine whether that element (or pair) is in tissue contact.Once the electrode elements in tissue-contact have been identified, theelectroporation generator energizes the identified electrode elements inaccordance with an electroporation energization strategy.

In one embodiment, the plurality of electrode elements is arranged in apie-shaped pattern forming a generally hemispherical-shaped distalsurface where the elements are separated from adjacent elements byrespective inter-element gaps. When this embodiment is used for eitherelectroporation-induced primary necrosis therapy orelectric-field-induced apoptosis (or secondary necrosis) therapy, theenergizing strategy carried out by the generator will corresponds tothese therapies (i.e., generate the appropriate pulse or pulses). Whenthis embodiment is used for electroporation-mediated therapy, inaddition the catheter may be configured with a lumen extendinglongitudinally through a shaft thereof to the electrode assembly andwhich is configured to deliver an electrolyte. The electrode assemblyincludes irrigation ports, which may comprise the inter-element gapsdescribed above (e.g., either open or occupied by a porous material).The electrolyte is delivered to the tissue site and enters the cellthrough the pores temporarily opened due to electroporation, modifying aproperty (e.g., a conduction characteristic) of the tissue to improve,for example, a subsequent ablation therapy. Alternatively, an outermostsurface of the electrode assembly may comprise chemical-elutingmaterials, which also enter the cell in the same manner and alter atissue property for a beneficial effect during a subsequent therapy. Thetissue sensing circuit may be further configured to confirm that apredetermined modification of a tissue property has occurred, inaccordance with the chosen electroporation therapy.

In another embodiment, the plurality of electrode elements are arrangedin at least a first array disposed on an outer surface of a tubular baseformed of electrically-insulating material. The array may extend along afirst path having a shape substantially matching that of the base. Theelectroporation generator is configured to selectively energizeidentified electrode elements of the array in a bipolar fashion so as toproduce a lesion (e.g., a narrow, linear lesion when the array has astraight shape). In an alternate embodiment, a second array is providedon the tubular base where the generator selectively energizes elementsfrom both arrays in a bipolar or multi-polar fashion to produce a widerlesion. The shape may be selected from the group comprising a linearshape, an arcuate shape, a L-shape, a question-mark shape or a spiralshape or any other medically useful shape.

In still further embodiments, the plurality of electrode elements arearranged in a plurality of arrays (multi-array) disposed on a baseformed of electrically-insulating material. The arrays may be arrangedin a fan-shaped pattern or other medically-useful patterns that areconfigured to produce a distributed or wide area lesion. In all theembodiments of the first aspect of the disclosure, the conductiveelement detector, preferably using the tissue sensing circuit,identifies those electrode elements that are in contact with tissuewherein the electroporation generator energizes only those elements,thereby improving selectivity in what tissue areas are subjected to thetherapy. In addition, the tissue sensing circuit may be used to confirmthat a tissue property has be modified in accordance with the chosenelectroporation therapy.

In a second aspect, the disclosure is directed to a system for opticallymonitoring electroporation therapy at a tissue site, and which involvesfirst delivering an electrochromic dye to or at the target tissue site(which delivery may be achieved either in situ or systemically). Themonitoring system includes a light source, an optical detector, acatheter carrying first and second optic fibers and a light analyzer.The light source is configured to generate a first light signal. Thefirst optic fiber is transmits the first light signal to its distal endand is directed towards (i.e., is incident upon) the tissue site. Thesecond optic fiber is configured to transmit a second light signalacquired at the tissue site (at its distal end) to the optical detector.The optical detector is configured to detect the second light signal andproduce a corresponding output signal. The light analyzer configured to(i) assess the detector output signal at a first time after anelectrochromic dye has been delivered to or applied at the tissue sitebut before an electric field has been applied in order to establish afirst, baseline optical characteristic of the second (received) lightsignal; (ii) monitor the detector output signal at a second time afterthe electric field has been applied to determine a second opticalcharacteristic that exhibits a color change indicative of an opticalradiation storm that accompanies a desired electric field strength; and(iii) monitor the detector output signal at a third time after thesecond time (e.g., after the electric field has been discontinued) for athird optical characteristic having an intensity that is reducedrelative to that of the baseline, which is indicative of an opticalblack-out representing an effective electroporation therapy. Through theforegoing, the progress of the therapy can be confirmed as well as theultimate success.

In a third aspect, the disclosure is directed to a temperature sensingcatheter system that involves the use of thermochromic or thermotropicmaterials. The system includes a light source, an optical detector, anelectrode catheter and an analyzer. The light source is configured togenerate a first light signal. The electrode catheter includes (i) ashaft having proximal and distal ends; (ii) an electrode disposed at thedistal end of the shaft where the electrode has a body with an outersurface and a cavity defining an inner surface; and (iii) an opticfiber. At least one of the cavity or the inner surface comprises athermochromic or thermotropic material configured to change color as afunction of temperature. The optic fiber has a distal end that is inoptical communication with the cavity and a proximal end. The opticfiber transmits the first light signal (from the light source) to itsdistal end where it is projected towards the cavity. The optic fiber isfurther configured to carry a second light signal acquired at its distalend back to its proximal end. The optical detector is configured todetect the second light signal and produce a corresponding outputsignal. The analyzer is configured to assess the detector output signaland generate a temperature signal indicative of the electrodetemperature. In an embodiment, the analyzer may use predeterminedcalibration data that correlates a received light spectrum to atemperature.

In further embodiments, at least a portion of the inner surface of thecavity comprises a layer of the thermally-sensitive material (i.e., thethermochromic or thermotropic material) or at least a portion of theinner surface of the cavity is impregnated with the thermally-sensitivematerial. In another embodiment, a distal lumen of the optic fiber isfilled with the thermally-sensitive material such that the optic fiberoptic distal end is in optical communication with the thermallysensitive material.

These and other benefits, features, and capabilities are providedaccording to the structures, systems, and methods depicted, describedand claimed herein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic and block diagram view of a system incorporatingembodiments for electroporation therapy involving direction-sensitivemulti-polar or multi-array catheter electrode assemblies.

FIGS. 2-4 are isometric and plan views of a direction-sensitivemulti-polar tip electrode assembly.

FIGS. 5A-5D and FIGS. 6-7 are isometric and plan views ofdirection-sensitive multi-polar electrode assemblies for creating linearlesions using bi-poles from the same electrode element line.

FIGS. 8-10 are isometric and plan views of a direction-sensitivemulti-polar electrode assembly for creating linear lesions usingbi-poles from spaced, parallel electrode element lines.

FIGS. 11-13 are isometric and plan views of a first embodiment ofmulti-polar multi-array electrode assembly for creating distributed orwide area lesions.

FIGS. 14-17 are isometric and plan views of a second embodiment ofmulti-polar multi-array electrode assembly for creating distributed orwide area lesions.

FIG. 18 is a diagrammatic and block diagram view of a system foroptical-based tissue sensing for electroporation therapy.

FIG. 19 is flowchart of a method for optical-based tissue sensing forelectroporation therapy.

FIGS. 20-21 are partial cross-sectional views of fiber optic temperaturesensing system embodiments.

DETAILED DESCRIPTION OF THE INVENTION

Referring now to the drawings wherein like reference numerals are usedto identify identical components in the various views, FIG. 1 is adiagrammatic and block diagram view of a system 10 in connection withwhich direction-sensitive multi-polar or multi-array electrodeassemblies for electroporation therapy may be used. In general, thevarious embodiments include an electrode assembly disposed at the distalend of a catheter. The electrode assembly comprises a plurality ofindividual, electrically-isolated electrode elements. Each electrodeelement is individually wired such that it can be selectively paired orcombined with any other electrode element to act as a bipolar or amulti-polar electrode for both sensing (more below) and electroporationenergization purposes. FIGS. 2-17 show various embodiments featuringdirection-sensitive multi-polar or multi-array electrode assemblies. Inthe sensing mode, the electrode elements are electrically scanned todetect or identify which electrode elements (or pairs) have electricalconduction characteristics indicative of contact with the target tissue(e.g., impedance, phase angle, reactance). Once such electrode elementshave been identified, an electroporation generator is controlled toenergize the identified electrode elements in accordance with anelectroporation energization strategy. The selective energizationimproves selectivity of the target tissue, more effectively directingthe therapy to just the desired, target tissue. The particularenergization strategy chosen will depend on the particular type ofelectroporation therapy sought to be achieved. Exemplary electroporationtherapies include: (1) electroporation-mediated therapy; (2)electroporation-induced primary necrosis therapy; and (3) electricfield-induced apoptosis (or secondary necrosis) therapy. Each therapywill be described below.

Electroporation-mediated ablation therapy refers to delivering tissuepre-conditioning effects using electroporation. Pre-conditioning effectswould lead to altering the biophysical properties of the tissue whichwould make the tissue receptive to other ablative therapies such asradio-frequency (RF), ultrasound, and photodynamic therapy. Tissuepre-conditioning may be achieved by delivering electrolytes to thetissue locally using electroporation, thereby changing the biophysicalproperties of the tissue such as its electrical, acoustical, optical,thermal, and perfusion properties. In this case, the electric fieldapplied to the tissue causes transient and reversible effects oftemporarily opening the pores on the cell wall, and the cell remainsviable after the application of the electric field. In general,electroporation will involve the application of direct current (DC) orvery low frequency alternating current (AC) to create an electric fieldsufficient to “tear” the lipid bilayer that forms the cell membrane.There are many voltage level/pulse duration/duty cycle combinations thatmay be effective (e.g., in one instance involving embryonic chickhearts, the tissue was placed between electrodes spaced 0.4 cm apart andsubjected to a series of 200 V/cm electrical stimuli from a commercialstimulator where varying numbers of 10 millisecond pulses were applied10 seconds apart). It should be understood that a plurality of factorsmay affect the particular energization scheme needed to achieve thetemporary (i.e., transient and reversible) opening of pores on the cellwall, including species, tissue size, cell size and development stage.

Electroporation-induced primary necrosis therapy refers to the effectsof delivering electrical current in such manner as to directly cause anirreversible loss of plasma membrane (cell wall) integrity leading toits breakdown and cell necrosis. This mechanism of cell death may beviewed as an “outside-in” process, meaning that the disruption of theoutside wall of the cell causes detrimental effects to the inside of thecell. Typically, for classical plasma membrane electroporation, electriccurrent is delivered as a pulsed electric field in the form ofshort-duration direct current (DC) pulses (e.g., 0.1 to 20 ms duration)between closely spaced electrodes capable of delivering a relatively lowelectric field strength of about 0.1 to 1.0 kV/cm.

Electric-field-induced apoptosis (or secondary necrosis) therapy refersto the effects of delivering electrical current in such a manner as tocause electromanipulation of the intracellular structures (e.g., such asthe nucleus, mitochondria or endoplasmic reticulum) and intracellularfunctions that precede the disassembly of the cell and irreversible lossof plasma membrane (cell wall). This mechanism of cell death may beviewed as an “inside-out” process, meaning that the disruption of theinside of the cell causes detrimental “secondary” effects to the outsidewall of the cell. For electric field-induced apoptosis, electric currentis delivered as a pulsed electric field in the form of extremelyshort-duration DC pulses (e.g., 1 to 300 ns duration) between closelyspaced electrodes capable of delivering a relatively high electric fieldstrength of about 2 to 300 kV/cm.

It should be understood that while the energization strategies forelectroporation-mediated ablation therapy, electroporation-inducedprimary necrosis therapy, electric-field-induced apoptosis (or secondarynecrosis) therapy are described as involving DC pulses, embodiments mayuse variations and remain within the spirit and scope of the invention.For example, exponentially-decaying pulses, exponentially-increasingpulses, mono-phase or bi-phase pulses and combinations of one or moreall may be used.

Accordingly, the electroporation embodiments described and depictedherein involve two different modes of therapy: (1) usage ofelectroporation therapy to destroy tissue (i.e., cell death) and (2)electroporation-mediated therapy where electroporation mechanism is usedto modify a tissue property (e.g., conductivity, reactance,responsiveness/irresponsiveness to photonic energy,responsiveness/irresponsiveness to ultrasonic energy, etc.) forsubsequent tissue sensing and/or ablation (e.g., via electrical tissuesensing or electrical energy delivery such as RF energy deliver, viaphotodynamic-based sensing and/or energy delivery, via ultrasound-basedsensing and/or energy delivery, etc.).

As to the first mode of therapy mentioned above (i.e., electroporationalone), it should be understood that electroporation is notsubstantially energy-dissipative and thus does not substantiallythermally alter the target tissue (i.e., does not substantially raiseits temperature), thereby avoiding possible thermal effects (e.g.,possible pulmonary vein stenosis when using RF energy for a pulmonaryvein isolation (PVI) procedure). Even to the extent that RF energy basedablation is used only as a “touch up” after an initial round ofelectroporation therapy, the thermal effects are reduced due to thecorresponding reduction in the application of RF energy. This “coldtherapy” thus has desirable characteristics.

As to the second mode mentioned above (i.e., electroporation-mediatedtherapy), electrochromic dyes may be used for effective monitoring ofthe progress of and completion of electroporation therapy to conditionthe target tissue. In the first mode, however, the use of electrochromicdyes do not come into play.

With this background, and now referring again to FIG. 1, the system 10includes a direction-sensitive multi-polar or multi-array catheterelectrode assembly 12 configured to be used as briefly outlined aboveand as described in greater detail below. The electrode assembly 12 isincorporated as part of a medical device such as a catheter 14 forelectroporation therapy of tissue 16 in a body 17 of a patient. In theillustrative embodiment, the tissue 16 comprises heart or cardiactissue. It should be understood, however, that embodiments may be usedto conduct electroporation therapy with respect to a variety of otherbody tissues.

FIG. 1 further shows a plurality of patch electrodes designated 18, 19,20 and 21, which are diagrammatic of the body connections that may beused by the various sub-systems included in the overall system 10, suchas a detector 22, a tissue sensing circuit 24, an energization generator26 (e.g., electroporation and/or ablation depending on the embodiment),an EP monitor such as an ECG monitor 28 and a localization andnavigation system 30 for visualization, mapping and navigation ofinternal body structures. It should be understood that the illustrationof a single patch electrode is diagrammatic only (for clarity) and thatsuch sub-systems to which these patch electrodes are connected may, andtypically will, include more than one patch (body surface) electrode.The system 10 may further include a main computer system 32 (includingan electronic control unit 50 and data storage—memory 52), which may beintegrated with the system 30 in certain embodiments. The system 32 mayfurther include conventional interface components, such as various userinput/output mechanisms 34 a and a display 34 b, among other components.

The detector 22 is coupled to the plurality of electrode elements of theelectrode assembly 12 and in one embodiment is configured to identifywhich elements have characteristics (e.g., if electricalcharacteristics, then for example, impedance, phase angle, reactance,etc.) indicative of contact of the electrode element with tissue 16. Inembodiments where the electrode elements cover up to 360 degrees (e.g.,a distal tip in hemispherical shape), it is desirable to energize onlythose electrode elements that are in contact with tissue, as describedabove. This may be thought of as a “direction-sensitive” sincedetermining what electrode elements are in contact with tissue alsodetermines the “direction” of the therapy to be delivered to the tissue.

A tissue sensing circuit 24 may be used in connection with the detector22 for determining an characteristic (e.g., electrical characteristic)to be used in making a “contact” versus “no contact” decision for eachelectrode element (or pair thereof). In an embodiment, the detector 22may be configured to scan (probe) the electrode elements (or pairs) andrecord the identification of such in-contact electrode elements. Thedetector 22, the tissue sensing circuit 24 and the generator 26 areenclosed in a dashed-line box in FIG. 1 to indicate the contemplatedcooperation necessary to perform the functions described herein.However, it should be understood that no necessary physical integrationis implied (i.e., these blocks may be embodied as physically separatecomponents). More particularly, any one of the detector 22, the tissuesensing circuit or the generator 26 may be implemented as a stand-alonecomponent or may be implemented in another portion of system 10 providedsuch other portion has adequate capabilities to perform the desiredfunction(s).

The tissue sensing circuit 24 as noted above is configured to determinean electrical characteristic associated with an electrode element orpair for purposes of determining whether the electrode element (or pair)is in contact with the tissue 16. The characteristic, when electrical innature, may be an impedance, a phase angle, a reactance or an electricalcoupling index (ECI), as seen by reference to co-pending U.S. patentapplication Ser. No. 12/622,488, filed Nov. 20, 2009 entitled “SYSTEMAND METHOD FOR ASSESSING LESIONS IN TISSUE” (Docket No. 0G-044003US(065513-0251)), owned by the common assignee of the present inventionand hereby incorporated by reference in its entirety. In such anembodiment, multiple skin patch electrodes may be used. Skin (bodysurface) patch electrodes may be made from flexible, electricallyconductive material and are configured for affixation to the body 17such that the electrodes are in electrical contact with the patient'sskin. In one embodiment, the circuit 24 may comprise means, such as atissue sensing signal source (not shown), for generating an excitationsignal used in impedance measurements (e.g., the excitation signal beingdriven through the subject electrode element) and means, such as acomplex impedance sensor (not shown), for determining a compleximpedance or for resolving the detected impedance into its componentparts. Other patch electrodes (shown only diagrammatically as electrode19) may preferably be spaced relatively far apart and function asreturns for an excitation signal generated by the tissue sensing circuit24 (as described in U.S. application Ser. No. 12/622,488). As tospacing, tissue sensing patch electrodes (shown only diagrammatically aselectrode 19) may be two in number located respectively on the medialaspect of the left leg and the dorsal aspect of the neck or mayalternatively be located on the front and back of the torso or in otherconventional orientations. Of course, other implementations arepossible.

The detector 22 may receive the measured characteristic from tissuesensing circuit 24 and then determine whether the subject electrodeelement is in tissue contact based on the value of the determinedelectrical characteristic, along with predetermined threshold data anddecision rules (e.g., if computer-implemented, programmed rules). Asshown, the tissue sensing circuit 24 may be coupled through thegenerator 26 and may use the same conductors to the electrode assembly12 for excitation purposes as used by the generator 26 for energizationpurposes.

The electroporation generator 26 is configured to energize theidentified electrode elements in accordance with an electroporationenergization strategy, which may be predetermined or may beuser-selectable. The generator 26 may be configured to communicate withthe detector 22 to receive a signal or data set indicative of theelectrode elements previously identified during the scanning phase asbeing in tissue contact. The electroporation energizing strategies(e.g., bi-poles, multi-poles, pulse magnitude, number and duration,etc.) are defined based on their correspondence to a respective one ofthe electroporation therapies described above, namely: (1)electroporation-mediated therapy; (2) electroporation-induced primarynecrosis therapy; and (3) electric field-induced apoptosis (or secondarynecrosis) therapy.

For electroporation-mediated therapy, the generator 26 may be configuredto produce an electric current that is delivered via the electrodeassembly 12 as a pulsed electric field in the form described above.

For electroporation-induced primary necrosis therapy, the generator 26may be configured to produce an electric current that is delivered viathe electrode assembly 12 as a pulsed electric field in the form ofshort-duration direct current (DC) pulses (e.g., 0.1 to 20 ms duration)between closely spaced electrodes capable of delivering a relatively lowelectric field strength (i.e., at the tissue site) of about 0.1 to 1.0kV/cm.

For electric field-induced apoptosis therapy, the generator 26 may beconfigured to produce an electric current that is delivered via theelectrode assembly 12 as a pulsed electric field in the form ofextremely short-duration direct current (DC) pulses (e.g., 1 to 300 nsduration) between closely spaced electrodes capable of delivering arelatively high electric field strength (i.e., at the tissue site) ofabout 2 to 300 kV/cm.

In certain other embodiments (e.g., electroporation-mediated ablationtherapy), both electroporation specific energy as well as ablationspecific energy will be used in the overall process and in suchembodiments, the generator 26 may be further configured to deliverablation energy as well, or another device may be provided to supply theablation energy.

For example, in the case of electroporation-mediated ablation therapy(i.e., electroporation to modify tissue characteristics then followed byRF ablation), the generator 26 may be further configured to generate,deliver and control RF energy output by the electrode assembly 12 of thecatheter 14. An ablation energizing power source portion of generator 26may comprise conventional apparatus and approaches known in the art,such as may be found in commercially available units sold under themodel number IBI-1500T RF Cardiac Ablation Generator, available fromIrvine Biomedical, Inc. In this regard, the ablation functional portionof the generator 26 may be configured to generate a signal at apredetermined frequency in accordance with one or more user specifiedparameters (e.g., power, time, etc.) and under the control of variousfeedback sensing and control circuitry as is known in the art. Forexample, the RF ablation frequency may be about 450 kHz or greater, incertain embodiments. Various parameters associated with the ablationprocedure may be monitored including impedance, the temperature at thetip of the catheter, ablation energy and the position of the catheterand provide feedback to the clinician regarding these parameters. As toablation therapy, the electrode 18 may function as an RFindifferent/dispersive return for an RF ablation signal (in certainembodiments).

With continued reference to FIG. 1, as noted above, the catheter 14 maycomprise functionality for electroporation and in certain embodiments(i.e., electroporation-mediated ablation therapy) also an ablationfunction (e.g., RF ablation). It should be understood, however, that inthose embodiments, variations are possible as to the type of ablationenergy provided (e.g., cryoablation, ultrasound, etc.). For example, theembodiment shown in FIG. 1 includes a fluid source 36 having abiocompatible fluid such as saline or other electrolyte suitable for theelectroporation-mediated therapy chosen, which may be delivered througha pump 38 (which may comprise, for example, a fixed rate roller pump orvariable volume syringe pump with a gravity feed supply from the fluidsource 36 as shown) for delivery of a suitable electrolyte forelectroporation-mediated ablation or saline for irrigation.

In the illustrative embodiment, the catheter 14 includes a cableconnector or interface 40, a handle 42, a shaft 44 having a proximal end46 and a distal 48 end. As used herein, “proximal” refers to a directiontoward the end of the catheter near the clinician and “distal” refers toa direction away from the clinician and (generally) inside the body of apatient. The catheter 14 may also include other conventional componentsnot illustrated herein such as a temperature sensor, additionalelectrodes, and corresponding conductors or leads. The connector 40provides mechanical, fluid and electrical connection(s) for cables 54,56 extending from the pump 38 and the generator 24. The connector 40 maycomprise conventional components known in the art and as shown may isdisposed at the proximal end of the catheter 14.

The handle 42 provides a location for the clinician to hold the catheter14 and may further provide means for steering or the guiding shaft 44within the body 17. For example, the handle 42 may include means tochange the length of a guidewire extending through the catheter 14 tothe distal end 48 of the shaft 44 or means to steer the shaft 44. Thehandle 42 is also conventional in the art and it will be understood thatthe construction of the handle 42 may vary. In an alternate exemplaryembodiment, the catheter 14 may be robotically driven or controlled.Accordingly, rather than a clinician manipulating a handle toadvance/retract and/or steer or guide the catheter 14 (and the shaft 44thereof in particular), a robot is used to manipulate the catheter 14.

The shaft 44 is an elongated, tubular, flexible member configured formovement within the body 17. The shaft 44 is configured to support theelectrode assembly 12 as well as contain associated conductors, andpossibly additional electronics used for signal processing orconditioning. The shaft 44 may also permit transport, delivery and/orremoval of fluids (including irrigation fluids and bodily fluids),medicines, and/or surgical tools or instruments. The shaft 44 may bemade from conventional materials such as polyurethane and defines one ormore lumens configured to house and/or transport electrical conductors,fluids or surgical tools. The shaft 44 may be introduced into a bloodvessel or other structure within the body 17 through a conventionalintroducer. The shaft 44 may then be advanced/retracted and/or steeredor guided through the body 17 to a desired location such as the site ofthe tissue 16, including through the use of guidewires or other meansknown in the art.

The localization and navigation system 30 may be provided forvisualization, mapping and navigation of internal body structures. Thesystem 30 may comprise conventional apparatus known generally in the art(e.g., an EnSite NAVX™ Navigation and Visualization System, commerciallyavailable from St. Jude Medical, Inc. and as generally shown withreference to commonly assigned U.S. Pat. No. 7,263,397 titled “Methodand Apparatus for Catheter Navigation and Location and Mapping in theHeart,” the entire disclosure of which is incorporated herein byreference). It should be understood, however, that this system isexemplary only and not limiting in nature. Other technologies forlocating/navigating a catheter in space (and for visualization) areknown, including for example, the CARTO navigation and location systemof Biosense Webster, Inc., the AURORA® system of Northern Digital Inc.,commonly available fluoroscopy systems, or a magnetic location systemsuch as the gMPS system from Mediguide Ltd. In this regard, some of thelocalization, navigation and/or visualization system would involve asensor be provided for producing signals indicative of catheter locationinformation, and may include, for example one or more electrodes in thecase of an impedance-based localization system, or alternatively, one ormore coils (i.e., wire windings) configured to detect one or morecharacteristics of a magnetic field, for example in the case of amagnetic-field based localization system.

FIGS. 2-4 are isometric and plan views of a direction-sensitivemulti-polar electrode assembly, in one embodiment designated electrodeassembly 12 a. The electrode assembly 12 a includes a plurality ofelectrically-conductive electrode elements 58 ₁, 58 ₂, . . . , 58 _(n)that are separated from adjacent elements by respective inter-elementgaps, shown at 60. The electrode elements 58 ₁, 58 ₂, . . . , 58 _(n)may be left open (i.e., unobstructed) or filled with porous material,for example, for irrigation purposes, or may alternatively be sealedwith electrically-insulative filler material. In the illustrativeembodiment, the electrode elements 58 ₁, 58 ₂, . . . , 58 _(n) arearranged in a pie-shaped pattern where all the individual electrodeelements are approximately the same size and shape. In one embodiment,the distal surface of electrode assembly 12 a may be rounded (e.g.,partially spherical or hemispherical), although other configurations maybe used. The individual elements 58 ₁, 58 ₂, . . . , 58 _(n) are furtherarranged so that collectively they form a proximally-facing shoulderportion 62. In addition, the electrode assembly 12 a has aproximally-extending stub 64 (best shown in FIG. 3) having a firstdiameter that reduced relative to the a second diameter of the outermostsurface of the pie-shaped pattern of electrode elements 58 ₁, 58 ₂, . .. , 58 _(n).

The electrode elements 58 ₁, 58 ₂, . . . , 58 _(n) may compriseconventionally employed electrically-conductive materials, such as,generally, metals or metal alloys. Examples of suitable electricallyconductive materials include (but are not limited to) gold, platinum,iridium, palladium, stainless steel, and various mixtures, alloys andcombinations thereof. In alterative embodiments, the electrode elements58 ₁, 58 ₂, . . . , 58 _(n) may comprise a so-called conforming (brush)electrode configuration, as seen by reference to U.S. Pat. No. 7,326,204to Paul et al. entitled “BRUSH ELECTRODE AND METHOD FOR ABLATION”(Docket No.: 0B-045301US), owned by the common assignee of the presentinvention and the entire disclosure of which is hereby incorporated byreference herein. Paul et al. disclose, generally, an electricallyconductive electrode formed from a plurality of flexible filaments orbristles for applying ablative energy (e.g., RF energy) and facilitateselectrode-tissue contact in target tissue having flat or contouredsurfaces. Other electrode configurations known in the art may also beused in the electroporation systems described herein.

FIG. 4 is a partial, cross-sectional view of the electrode assembly 12 ain contact with tissue 16. In a first embodiment, the system 10,including the electrode assembly 12 a, may be used for a methodinvolving either electroporation-induced primary necrosis therapy orelectric field-induced apoptosis therapy (or secondary necrosistherapy).

The method begins with a clinician, such as a physician, maneuvering thecatheter 14, including the electrode assembly 12 a, to the desired sitewhere tissue 16 is located. In this regard, previous mapping exercisesmay have been conducted which has resulted in a map of the patient'sanatomy that will be the subject of the electroporation therapy. Such amap may be used in navigating the catheter 14 to the site. Once at thesite, the physician controls the catheter 14 such that the distal end ofthe electrode assembly 12 a is against the tissue 16.

The next step involves identifying which electrode elements 58 ₁, 58 ₂,. . . , 58 _(n) are in contact with the tissue, using the detector 22and the tissue sensing circuit 24, as described above. The detector 22may record the identification of the electrode elements 581, 58 ₂, . . ., 58 _(n) (or pairs thereof) for subsequent use in controllingenergization during the electroporation therapy. In the illustrativeexample in FIG. 4, the electrode elements identified as being in contactwith the tissue 16 include electrode elements 58 ₁ and 58 ₂.

The next step involves energizing the identified electrode elements(i.e., those elements that are in contact with tissue—namely, electrodeelements 58 ₁ and 58 ₂ in the example of FIG. 4) using theelectroporation generator 26 in accordance with an energizationstrategy. The energization strategy used in turn will be based on thechosen electroporation therapy. In this first embodiment, the therapiesinclude either electroporation-induced primary necrosis therapy orelectric field-induced apoptosis therapy (or secondary necrosistherapy). Accordingly, the generator 26 is controlled to deliverelectrical energy consistent with the electrical parameters describedabove to perform each of these therapies. The energization strategy ispreferably conducted in a bipolar fashion (i.e., electrode element toelectrode element), which creates local electric fields, designatedfields 66. The established, local electric fields cause the desiredeffect on the tissue cells in accordance with the chosen electroporationtherapy.

The next step involves determining whether the sought-after modificationto a property of the target tissue 16 has occurred. Preferably, thisstep is also performed using tissue sensing circuit 24. Depending on theproperty sought to be modified, achieving the desired propertymodification can be confirmed by a physician monitoring a readout or thelike of the measured or computed tissue property of interest (e.g., aread-out from the tissue sensing circuit 24 or display that is incommunication with the tissue sensing circuit). In an alternateembodiment, the tissue sensing circuit 24 (or other component viasuitable communication) may be configured to generate a signalindicative of when the desired tissue modification has been achieved(e.g., a pre-set threshold). Once the desired modification to the tissueproperty has been achieved, the electroporation therapy to the targettissue 16 can be discontinued (i.e., the applied electric fielddiscontinued).

In one embodiment, the system is configured such that a tissue propertyis monitored substantially continuously during therapy (i.e., the tissuesensing circuit 24 is configured to monitor the tissue property ofinterest concurrently with electric field generation). In thisembodiment, the physician is able to use real time feedback to determinewhen to discontinue the therapy. In an alternate embodiment, the systemmay be configured to blank the tissue sensing circuit 24 output duringhigh voltage switching of the electroporation generator. The foregoingassumes that the sensing circuit 24 is based on electrical measurementstaken from electrodes. In a still further embodiment, the sensingcircuit may be light based and thus immune from high voltageinterferences produced by virtue of the electroporation generator, sinceany light-to-voltage converters will be located outside the body,thereby isolating the downstream electronics from the interference. In astill further embodiment, the method is sequential, where the physicianswitches between applying power (therapy) and tissue sensing (propertymeasurement) and continues iterating until completion (e.g.,energize-check tissue property, energize-check tissue property,energize-check tissue property, etc.). In yet another embodiment, thephysician will check the tissue property (using tissue sensing circuit24) after completing a predefined instance of therapy (e.g., X minutesof therapy at predetermined conditions).

With continued reference to FIGS. 2-4, the electrode assembly 12 a maybe used in an alternate way for performing electroporation-mediatedablation therapy. In this regard, the electrode assembly 12 a is used toeffect transient and reversible electroporation, along with the deliveryof a suitable chemical adapted to improve subsequent therapy such as RFablation. Accordingly, in this alternate embodiment, the electrodeassembly 12 a, with the exception of the changes to be described below,may the same as described above. The electrode assembly 12 a may beconfigured to deliver a chemical, which may be for example anelectrolyte 68 (FIGS. 3 and 4) in proximity to the tissue 16.

In the case of delivery of a liquid chemical (electrolyte), the shaft 44may include at least one lumen (omitted for clarity) extendinglongitudinally therethrough to carry the electrolyte 68 from a source 36(FIG. 1) to the electrode assembly 12 a. The electrode assembly 12 aincludes a channel 70 intermediate the lumen (not shown) and one or moreirrigation ports on the distal surface of the electrode assembly 12 a.The channel 70 may comprise either the inter-element gaps 60 (free ofany material), the inter-elements gaps 60 (filled with a porousmaterial) or one ore more dedicated passages (not shown) through one ormore of the electrode elements 58 ₁, 58 ₂, . . . , 58 _(n) whichterminate in discrete irrigation ports on the distal surface.

In an alternate embodiment, the chemical is delivered locally. Forexample, the outermost, distal surface of the electrode assembly 12 amay comprise a chemical-eluting material, shown by arrows 72 in FIG. 4(eluting from the distal surface of the electrode assembly 12). Moreparticularly, at least one of either the outermost surface of theelectrode elements 58 ₁, 58 ₂, . . . , 58 _(n) or the outermost surfaceof a material used to fill in the inter-element gap 60 may be modifiedto exhibit chemical-eluting properties. The chemicals involved in theembodiment comprise those adapted to modify a property of the targettissue 16. As an example, the property may be an electrical conductivityproperty of the target tissue, such as the fat pads of the ganglionatedplexi, which modification renders the target tissue more receptive andamenable to conduction of RF current as used in RF ablation.

With reference to FIG. 4, a method of electroporation-mediated ablationtherapy will now be set forth. An initial step of the method involvesconfiguring the electrode assembly 12 a with a chemical efflux/elutingcapability, as described above. The next step involves maneuvering thecatheter, in particular the electrode assembly 12 a thereof, to thetarget tissue site 16, again as described above. Next, identifying whichelectrode elements 58 ₁, 58 ₂, . . . , 58 _(n) are in contact with thetissue 16, again as already described above, using the detector 22 andthe tissue sensing circuit 24.

The next step involves energizing the identified electrode elements(i.e., those elements that are in contact with tissue—namely, electrodeelements 58 ₁ and 58 ₂ in the example of FIG. 4) using theelectroporation generator 26 in accordance with a suitable energizationstrategy. The energization strategy used by the generator 26 in thisembodiment will be based on electroporation-mediated ablation therapydescribed above. Accordingly, the generator 26 is controlled to deliverelectrical energy consistent with the electrical parameters describedabove to cause transient and reversible electroporation. Theenergization strategy is preferably conducted in a bipolar fashion(i.e., electrode element to electrode element), which creates localelectric fields that are shown and designated as fields 66. The electricfield across the cell membrane is operative to open pores in the cellwall. Simultaneous with the energization step, one or both of (1) theelectrolyte 68 or (2) the predetermined chemical 72 are present in thevicinity of the target tissue. With the cell pores opening up due to theelectric field 66, either or both of the electrolyte 68 or the chemical72 are taken into (enter into) the cells of the target tissue to effectthe desired modification to at least one property of the target tissue.Again, in one example, the modification for purposes of a subsequent RFablation therapy involves modifying the electrical conductionproperties, of the target tissue 16 to be more receptive and amenable tocarrying RF current.

The next step involves determining whether the sought-after modificationto a property of the target tissue 16 has been effected. Preferably,this step is also performed using tissue sensing circuit 24. Dependingon the property sought to be modified, achieving the desired propertymodification can be confirmed by a physician monitoring a readout or thelike of the measured or computed tissue property of interest (e.g., aread-out from the tissue sensing circuit 24 or a display incommunication therewith). In an alternate embodiment, the tissue sensingcircuit 24 (or other component via suitable communication) may beconfigured to generate a signal indicative of when the desired tissuemodification has been achieved (e.g., a preset threshold). Once thedesired modification to the tissue property has been achieved, theelectroporation therapy to the target tissue 16 can be discontinued.

Finally, after the target tissue 16 has been modified, RF ablation isperformed on the target tissue 16. In this regard, the generator 26 mayinclude an RF ablation function or a separate RF ablationgenerator/controller may be used. In either case, in one embodiment, thesame electrode elements 58 _(i) that were identified and energized forelectroporation therapy are now energized for RF ablation. RF ablationmay conducted by energizing the identified electrode elements 58 _(i) ina bipolar fashion (i.e., RF energy being passed between identifiedelectrode elements 58 _(i), or pairs thereof), a multi-polar fashion ora unipolar fashion (i.e., between one or more of the identifiedelectrode elements 58 _(i) and a remote dispersive/indifferent skinpatch electrode such as electrode 18, and/or a dispersive electrode on acatheter inside the body, as seen by reference to PCT InternationalPatent Application PCT/US2006/061710 (see FIG. 21 and paragraph [00148];Docket No.: 0B-047812WO) and corresponding U.S. Patent Publication2008/0275465, Application Ser. No. 12/096,069 (Docket No.: 0B-047834US)entitled “DESIGN OF HANDLE SET FOR ABLATION CATHETER WITH INDICATORS OFCATHETER AND TISSUE PARAMETERS”, both owned by the common assignee ofthe present invention and the entire disclosures of both herebyincorporated by reference herein). Use of such a catheter electrodeinside the body may exhibit increased rejection of noise as compared toa body surface electrode. It should be appreciated that the art isreplete with configurations and strategies for ablation generally, andRF ablation in particular. Accordingly, the foregoing description isexemplary only and not limiting in nature.

FIGS. 5A-5D and FIGS. 6-7 show a direction-sensitive multi-polarelectrode assembly designated 12 b suitable for creating linear lesionsusing bi-poles in the same electrode element line. Unless otherwisedescribed below, the electrical connections and interactions with thecomponents of system 10 will be the same for assembly 12 b as was setforth above for assembly 12 a and will accordingly not be repeated.

The electrode assembly 12 b is configured to be disposed at the distalend 48 of catheter 14. The electrode assembly 12 b comprises a pluralityof electrode elements (poles) 74 ₁, 74 ₂, . . . 74 _(n) arranged in afirst array 76. The electrode elements 74 ₁, 74 ₂, . . . 74 _(n) of thearray 76 are distributed contiguously in a linear or arcuate fashion onan outermost surface of a base 78, which in the illustrative embodimentis configured as a tubular structure (see FIGS. 5A, 6-7). The tubularbase 78 comprises electrically-nonconductive material. The individualpoles 74 ₁, 74 ₂, . . . 74 _(n) are separated from each other byintervening gaps, which may be impervious or may contain ports or pores(not shown) for irrigation purposes.

The poles 74 ₁, 74 ₂, . . . 74 _(n) of array 76 extend along a firstpath 80 having a shape substantially matching that of the base 78. Inthe illustrative embodiment, the tubular base 78 has an axis 82 that isstraight such that the first path 80 is also straight and substantiallyparallel to axis 82. However, the tubular base 78 may, in alternateembodiments (i) be formed in material composition and structure so as tobe flexible enough to allow bending into a non-straight shapes; (ii)include mechanisms to impart a shape, such as for example pull wires orthe like; or (iii) have a preformed shape. Moreover, the tubular base 78of the electrode assembly 12 b may be shaped relative to the cathetershaft 44 (best shown in FIG. 2) as a substantially straight tube oralternatively, the tubular base 78 may have an arcuate shape such thatthe shaft/tubular base together take the shape of a hockey stick, aquestion mark or a spiral. In such other embodiments, the poles 74 ₁, 74₂, . . . 74 _(n) may be distributed on the first path 80 such that itsshape matches the shape of the arcuate or alternative shaped tubularbase 78.

Electrode assembly 12 b may include a further plurality of electrodeelements defining a second array 84. In the illustrative embodiment, theplurality of electrode elements (poles) of the second array 84 arearranged in a substantially linear fashion, parallel to the axis 82 andparallel to the path 80 along which the poles of the first array 76extend. In further embodiments, further arrays of electrode elements(poles) may be provided on the outer surface of the tubular base 78,preferably extending along a respective path that is parallel to theaxis 82 and also parallel to the other pole paths. Generally, theelectrode elements (poles) 74 ₁, 74 ₂, . . . 74 _(n) of the electrodeassembly 12 b may be formed so as to be substantially flush with theouter surface of the tubular base 78.

In a still further variation of the electrode assembly 12 b, the tubularbase 78 has an arcuate shape, designated base 78 a. As shown in FIGS.5B-5C, the arcuate tubular base 78 a has electrode elements (poles) 74₁, 74 ₂, . . 74 _(n) placed on the surface (plane) of the arc that isparallel to the longitudinal axis 82 a of the catheter shaft (and plane83 cutting through the electrodes is normal to axis 82 a), such as likea so-called Lineage PV to create pulmonary vein isolation lines withinthe pulmonary vein, as seen by reference to U.S. Patent Publication U.S.2006/0111708, application Ser. No. 11/328,565 filed Jan. 10, 2006entitled ABLATION CATHETER ASSEMBLY HAVING A VIRTUAL ELECTRODECOMPRISING PORTHOLES, owned by the common assignee of the presentinvention and hereby incorporated by reference in its entirety.Alternatively, as shown in FIG. 5D, the arcuate tubular base 78 a haselectrode elements (poles) 74 ₁, 74 ₂, . . . 74 _(n) placed on the face(plane) of the arc that is normal to the longitudinal axis 82 a of thecatheter shaft, such as a branding iron configuration, for creating alesion on the antrum of the pulmonary vein, as seen by reference to U.S.Patent Publication U.S. 2008/0161790, application Ser. No. 11/617,524filed Dec. 28, 2006 entitled VIRTUAL ELECTRODE ABLATION CATHETER WITHELECTRODE TIP AND VARIABLE RADIUS CAPABILITY, owned by the commonassignee of the present invention and hereby incorporated by referencein its entirety.

FIGS. 8-10 show an alternate construction of a direction-sensitivemulti-polar electrode assembly designated 12 c suitable for creatinglinear lesions. Again, unless otherwise described below, the electricalconnections and interactions with the components of the system 10 willbe the same for assembly 12 c as set forth above for assemblies 12 a, 12b and will accordingly not be repeated. The electrode elements (poles)74 ₁, 74 ₂, . . . 74 _(n) of the electrode assembly 12 c may be formedso as to be slightly raised relative to the outer surface of the tubularbase 78.

Referring to FIG. 5A, bi-poles may be formed by pairing and electricallyconnecting individual ones of the electrode elements (poles) 74 ₁, 74 ₂,. . . 74 _(n) taken from the same line (i.e., from the array 76 in FIG.5A). In this instance, the electric field formed by the energization ofthese bi-poles is shown as field lines 86 in FIG. 5A. However, referringto FIG. 8, bi-poles may also be formed by pairing and electricallyconnecting individual electrode elements (poles) taken from separate,parallel arrays. In this instance, the electric field formed by theenergization of these bi-poles is shown at 88 in FIG. 8. For reference,in both FIGS. 5A and 8, black electrode elements (poles) and whiteelectrode elements (poles) may be paired to form a bipole. It should beappreciated that by using the electrode assembly 12 b or 12 c andforming bi-poles from one line (one array of electrode elements orpoles), a narrow linear lesion may be produced. On the other hand, byusing electrode assembly 12 b or 12 c and energizing bi-poles from twoor more parallel arrays, a wider lesion may be produced. The width ofthe lesion will depend on the distance between the arrays (i.e.,distance between the paths along with the poles in each array extend).

With reference to FIGS. 5A-10, a method will now be described usingelectrode assemblies 12 b, 12 c to create linear lesions by way ofelectroporation-induced primary necrosis therapy or electricfield-induced apoptosis (or secondary necrosis) therapy. The first stepinvolves maneuvering the catheter, in particular the electrode assemblythereof, to the target tissue site 16, and placing the electrodeassembly 12 b, 12 c in contact against the tissue 16, all as alreadydescribed above. The next step involves identifying which electrodeelements (poles) 74 ₁, 74 ₂, . . . , 74 _(n) are in contact with thetissue 16, again as already described above, using the detector 22 andthe tissue sensing circuit 24.

The next step involves energizing the identified electrode elements(i.e., those elements that are in contact with tissue) using theelectroporation generator 26 in accordance with a suitable energizationstrategy. The energization strategy used in turn will be based on theelectroporation therapy chosen. In this embodiment, the therapiesinclude either electroporation-induced primary necrosis therapy orelectric field-induced apoptosis therapy (or secondary necrosistherapy). Accordingly, the generator 26 is controlled to deliverelectrical energy consistent with the electrical parameters describedabove to perform the selected one of these therapies. The energizationstrategy is preferably conducted in a bipolar fashion (i.e., electrodeelement to electrode element), which creates local electric fields, forexample only as shown by field designated 86 (FIG. 5A) or as designated88 (FIG. 8). The established, local electric fields are operative tocreate a linear lesion via electroporation-induced primary necrosis orelectric field-induced secondary necrosis. As described above, the widthof the legion may be controlled by energizing bipoles taken from onearray of electrode elements (narrow) or by energizing bipoles taken fromseparate (parallel) arrays. In addition, spot lesions are also possibleby selectively energizing electrodes proximal to and/or in contact withan ectopic site.

The next step involves determining whether the sought-after modificationto a property of the target tissue 16 has occurred. Preferably, thisstep is performed using the tissue sensing circuit 24. Depending on theproperty sought to be modified, achieving the desired propertymodification can be confirmed by a physician monitoring a readout or thelike of the measured or computed tissue property of interest (e.g., aread-out from the tissue sensing circuit 24 or a display incommunication therewith). In an alternate embodiment, the tissue sensingcircuit 24 (or other component via suitable communication) may beconfigured to generate a signal indicative of when the desired tissuemodification has been achieved (e.g., a preset threshold). Once thedesired modification to the tissue property has been achieved, theelectroporation therapy with respect to the target tissue 16 may bediscontinued.

With respect to FIGS. 5A-10, it should be understood that variations arepossible. For example, the illustrated multi-polar electrode assembliesmay comprise electrically conductive wires, rings, loops, and/or coilsembedded on the surface of the catheter body (e.g., the tubularstructure 78 or 78 a). These embedded wires, rings, loops and/or coilsmay be exposed at specific sites on the catheter body to create theconfigurations described in those figures.

FIGS. 11-13 show a direction-sensitive multi-polar multi-array electrodeassembly, designated 12 d, suitable for creating distributed or widearea lesions in accordance with an electroporation therapy. Unlessotherwise described below, the electrical connections and interactionsof electrode assembly 12 d with the components of system 10 will be thesame as described above for assemblies 12 a, 12 b and 12 c andaccordingly will not be repeated.

The electrode assembly 12 d is configured to be disposed at the distalend 48 of the catheter 14 and includes a base 90 comprisingelectrically-insulative (nonconductive) material. In the illustrativeembodiment, the base 90 includes eight branches in a fan-like(asterisk-shaped) pattern. The assembly 12 d further includes aplurality of electrode elements (poles) 92 arranged in a plurality ofarrays (multi-array), the arrays being designated 94 ₁, 94 ₂, . . . 94_(n) (best shown in FIG. 12) and arranged in manner corresponding tothat of the base, i.e., in a fan-like pattern configured to cover adistributed or wide area for creating a corresponding lesion. Theindividual poles 92 may be separated from each other by interveninggaps, which may be impervious or may contain ports or pores (not shown)for irrigation purposes. In addition, in one embodiment, the separationdistance between all the electrode elements (poles) may be approximatelyequal.

As shown in FIG. 13, the assembly 12 d may be generally planar. However,the base 90 need not be planar and may alternately be configured anddeployed as a pentagon array (“Pentarray”), an umbrella/parachute, anexpandable/retractable loop or a balloon. Moreover, the base 90 maycomprise a flex circuit configured to provide electrical connectionlines between the electrode elements and the various components of thesystem 10.

FIGS. 14-17 show a still further embodiment of electrode assembly(designated assembly 12 e) configured to be disposed at the distal endof catheter 14 where the base is configured and deployed as a pluralityof expandable/retractable loops. Unless otherwise described below, theelectrical connections and interactions with the components of thesystem 10 may be the same for assembly 12 e as was set forth above forany of the electrode assemblies 12 a-12 d and will accordingly not berepeated.

FIG. 14 is an isometric view of the assembly 14 shown in a deployedstate. During insertion of the catheter 14 that includes assembly 12 e,and while maneuvering the catheter 14 to the target site of the tissue16, the assembly 14 remains in a retracted state (not shown). Theelectrode assembly 12 e includes a plurality of loops 96 each of whichcarry one or more electrode elements 92. The expandable/retractableconstruction of assembly 12 e may utilize known approaches.

FIG. 15 is an isometric view showing, in greater detail , a portion thatis encircled in FIG. 14. FIG. 16 is a side, plan view of the assembly 12e while FIG. 17 is a top, plan view of the assembly 12 e.

With reference to FIGS. 11-17, a method will now be described usingelectrode assemblies 12 d, 12 e to create distributed or wide arealesions by way of electroporation-induced primary necrosis therapy orelectric field-induced apoptosis (or secondary necrosis) therapy. Thefirst step involves maneuvering the catheter, in particular theelectrode assembly thereof, to the target tissue site 16, and placingthe electrode assembly 12 d, 12 e in contact against the tissue 16 , allas already described above. The next step involves identifying whichelectrode elements (poles) 92 are in contact with the tissue 16, againas already described above, using the detector 22 and the tissue sensingcircuit 24.

The next step involves energizing the identified electrode elements(i.e., those elements that are in contact with tissue) using theelectroporation generator 26 in accordance with a suitable energizationstrategy. The energization strategy used in turn will be based on theelectroporation therapy chosen. In this embodiment, the therapiesinclude either electroporation-induced primary necrosis therapy orelectric field-induced apoptosis therapy (or secondary necrosistherapy). Accordingly, the generator 26 is controlled to deliverelectrical energy consistent with the electrical parameters describedabove to perform the selected one of these therapies. The energizationstrategy is preferably conducted in a bipolar fashion (i.e., electrodeelement to electrode element), which creates electric fields, shown inFIG. 11 as field 98 for one exemplary electrode element (pole) to itsnearest bipole neighbor elements. The electric field 98, whenestablished using bipoles throughout the assembly 12 d or 12 e, isoperative to create a distributed or wide area lesion viaelectroporation-induced primary necrosis or electric field-inducedsecondary necrosis.

The next step involves determining whether the sought-after modificationto a property of the target tissue 16 has been effected. Preferably,this step is performed using the tissue sensing circuit 24. Depending onthe property sought to be modified, achieving the desired propertymodification can be confirmed by a physician monitoring a readout or thelike of the measured or computed tissue property of interest (e.g., aread-out from the tissue sensing circuit 24 or a display incommunication therewith). In an alternate embodiment, the tissue sensingcircuit 24 (or other component via suitable communication) may beconfigured to generate a signal indicative of when the desired tissuemodification has been achieved (e.g., a preset threshold). Once thedesired modification to the tissue property has been achieved, theelectroporation therapy to the target tissue 16 may be discontinued.

FIG. 18 is a diagrammatic and block diagram of a system 110 forconfirming the delivery and effectiveness of electroporation therapy. Inthe illustrative embodiment, the system 110 employs optical-based tissuesensing and is used in connection with electrochromic dyes.Electrochromic dyes will be described in greater detail below; however,generally, a property of electrochromic dyes (e.g., its color) may becontrolled or modified in accordance with an electric field. Thisproperty is used by system 110. The target tissue 112 may compriseendocardial tissue within the heart of a human body. It should beunderstood, however, that the system 110 may find application inconnection with a variety of tissues within human and non-human bodies.

A method for confirming the delivery and effectiveness ofelectroporation generally includes a number of steps. The first stepinvolves applying the electrochromic dyes to the target tissue. The nextstep involves optically monitoring the dyes to establish a baselineoptical characteristic. The next step involves applying an electricfield in the vicinity of the tissue in accordance with an selectedelectroporation energization strategy. Finally, the method involvesdetecting changes in the monitored optical characteristic (e.g., of thetissue site after the dye has been delivered). For example, an intensecolor change can be indicative of an effective electric field or an“optical black out” can be indicative of a successful conclusion ofelectroporation therapy. These steps will be described in greater detailbelow, along with a description of suitable system components forperforming the method.

The system 110 includes a mechanism suitable for use in a catheter thatmay be used to carry light to and from the tissue 112, and to analyzethe light captured at the tissue site. In this regard, the system 110includes a deformable, tubular body 114 (e.g., a catheter), a pluralityof optic fibers including fibers 116, 118, an electromagnetic radiationsource 120 (i.e., light source), an electromagnetic radiation sensor 122(i.e., optical detector) and a control unit 124 (e.g., an electroniccontrol unit (ECU)).

The body 114 functions as a catheter and is provided to house fibers116, 118 for example as seen by reference to PCT InternationalApplication PCT/US09/39367 filed Apr. 2, 2009, published WO 2009/124220on Oct. 8, 2009 (Docket No. 0B-057501WO (065513-0212)) entitled“PHOTODYNAMIC-BASED MYOCARDIAL MAPPING DEVICE AND METHOD”, owned by thecommon assignee of the present invention and hereby incorporated byreference in its entirety. The body 114 may also allow removal of bodilyfluids or injection of fluids and medicine into the body. The body 114may further provide a means for transporting surgical tools orinstruments within a body. For example, the body 114 may house anelectrode (not shown) used in ablation of the tissue 112. The body 114may be formed from conventional materials such as polyurethane. The body114 is tubular and is deformable and may be guided within a body by aguide wire or other means known in the art. The body 114 has a proximalend 126 and a distal end 128 (as used herein, “proximal” refers to adirection toward the body of a patient and away from the clinician while“distal” refers to a direction toward the clinician and away from thebody of a patient). The body 114 may be inserted within a vessel locatednear the surface of a patient (e.g., in an artery or vein in the leg,neck, or arm) in a conventional manner and maneuvered to a region ofinterest 130 in the tissue 112.

The optic fibers 116, 118 are provided to transmit and receiveelectromagnetic radiation. The fibers 116, 118 are conventional and maybe made from various glass compositions (e.g., silica) or plastics(e.g., polymethyl methaacrylate (PMMA) surrounded by fluorinatedpolymers). The fibers 116, 118 include a core and a cladding with thecore having a higher refractive index than the cladding. The fibers 116,118 may further include a buffer layer and a jacket as is known in theart. The fibers 116, 118 may, for example, comprise any of a variety ofcommon fibers sold by Polymicro Technologies, Inc., Edmund Optics, Inc.,Keyence Corporation, or Mitsubishi International Corporation. The fibers116, 118 are disposed within the catheter body 114 and may extend fromthe proximal end 126 to the distal end 128.

The electromagnetic radiation source 120 is provided to generate a firstset of electromagnetic radiation for transmission through one or moreoptic fibers (i.e., a first light signal). In the illustratedembodiment, the source 120 transmits radiation through the fiber 116.The source 20 may comprise, for example, a light emitting diode (LED) orlaser (e.g., a laser diode). The source 120 may produce a monochromaticor spectral radiation and the radiation may be polarized or unpolarized.The source 120 may generate radiation at various points along theelectromagnetic spectrum including, for example, visible light,infrared, near infrared, ultraviolet and near ultraviolet radiation. Theradiation source 120 may emit radiation in a controlled mannerresponsive to signals Si received from the control unit 124. The source120 may be located at or near the proximal end of fiber 116 and/orproximal end 126 of the catheter body 114. The source 120 may produceboth radiation for diagnostic and ablative purposes, or only for onepurpose. Multiple sources may also be used, either in conjunction withthe same fibers or different fibers.

The electromagnetic radiation sensor 122 (i.e., optical detector) isprovided to generate a signal S₂ in response to a second set ofelectromagnetic radiation (i.e., a second light signal) received throughan optic fiber. In the embodiment illustrated in FIG. 18, the sensor 122receives radiation transmitted through fiber 118. Radiation receivedthrough the fiber 118 originates from the tissue 112 in response toradiation transmitted through the fiber 116 from the source 120. Thesensor 122 may comprise a photodiode. The sensor 122 may be located ator near the proximal end of fiber 118 and/or proximal end 126 of thecatheter body 114.

The control unit 124 generates one or more signals, designated S₁, toselectively activate the source 120. In response, the source 120generates a set of electromagnetic radiation (illustrated generally inFIG. 1 by solid arrows 132) that is transmitted through and out of thefiber 116 and projected toward and therefore incident upon the region ofinterest 130 of the tissue 12. Another set of electromagnetic radiation(illustrated generally in FIG. 1 by broken line arrows 134) originatesat the tissue 12 in response to the radiation 132 transmitted throughfiber 116, particularly altered by the presence of the electrochromicdyes. The radiation 134 originating from tissue 112 may comprise atleast a portion of radiation 132 reflected by the tissue 112. Inalternate embodiments, a filter 136 may be disposed within the returnfiber 118 or may cover the proximal or distal end of the fiber 118 tocontrol the passage of radiation 134 to the sensor 122 by permittingpassage of radiation of a selected wavelength (or range of wavelengths)while filtering out radiation 132 and optical noise. Other variationsare possible, including the use of a lens and/or other light modifyingstructures. Other embodiments suitable for carrying light to and fromthe tissue site are known in the art, for example as seen by referenceto PCT International Application WO/US08/87426 filed Dec. 18, 2008(Docket No. 0B-053601WO (065513-0175)) entitled “PHOTODYNAMIC-BASEDTISSUE SENSING DEVICE AND METHOD”, owned by the common assignee of thepresent invention and hereby incorporated by reference in its entirety.

The control unit 124 provides a means for selectively activating source120 to direct a set of electromagnetic radiation through the fiber 116to the tissue 112. The control unit 124 also provides a means forreceiving a signal S₂ generated by the sensor 122 in response to anotherset of electromagnetic radiation received through the fiber 118 andoriginating from or acquired at the region of interest 130 of the tissue112 in response to the radiation transmitted through fiber 116. Thecontrol unit 124 also provides a means 138 for analyzing the detectedsignal S₂ to assess the changes (if any) in the electrochromic dyesindicative of whether the electroporation therapy to the tissue 112 hasbeen effective or not. Among other things, the analyzer 138 establishesa baseline optical characteristic 140 before the electroporation therapyhas begun to provide a foundation against which changes can bedetermined and assessed. The optical characteristic 140 is the result ofthe analysis of the signal output from the sensor 122 and may correspondto one or more characteristics of the returned light signal 134. Thecontrol unit 124 may be further configured to output indications 142,including at least a first indication during electroporation therapythat the energizing strategy is producing an adequate electric field atthe tissue site, and a second indication when the electroporationtherapy has been carried on sufficiently to be deemed effective (i.e.,complete). The logic performed by the analyzer 138 in making theassessments will be described in greater detail below.

The control unit 124 may comprise a programmable microprocessor ormicrocontroller or may comprise an application specific integratedcircuit (ASIC). The control unit 124 may include a central processingunit (CPU) and an input/output (I/O) interface through which the controlunit 124 may receive a plurality of input signals including signalsgenerated by sensor 122 and generate a plurality of output signals toconvey information regarding characteristics of the tissue 112 (moreparticularly, characteristics of the second light signal acquired at thetissue site, from which various conclusions may be drawn, as describedherein). Alternatively, signals may be transmitted wirelessly in aconventional manner.

Embodiments of the system 110 also include a means or a system 144 fordelivering electrochromic dye 146 to the tissue 112. Electrochromic dyeschange color in response to changes in the electric field. The dye mayalso be capable of ablating the tissue. Embodiments make use of thisproperty to monitor the progress and ultimate success of electroporationtherapy. Examples of suitable electrochromic dyes includes fast-actingdyes, such as an electrochromic and potentiometric dye such asdi-4-ANEPPS and di-4-ANEPPQ, belonging to a structural class calledstyryl or naphthylstyryl. Certain electrochromic dyes are known for usein optical mapping applications.

Dye 146 may be applied to the tissue 112 in a variety of ways. Forexample, the dye 146 may be introduced locally (i.e., through in-situdelivery) or systemically (i.e., such as through injection into thecoronary artery). It should be understood that the system and method mayalso involve use of multiple electrochromic dyes 146.

Embodiments of the system 110 also include an electroporation system 148for providing a catheter-based device configured to establish anelectric field sufficient to cause electroporation in the tissue 112. Ingeneral, the system 148 includes electroporation electrodes at a distalend of the catheter and an electroporation generator configured toenergize the electroporation electrodes in accordance with anelectroporation energizing strategy. For example, any of the embodimentsof FIG. 1-17 described above may be used to conduct the desiredelectroporation therapy, as well as other configurations known in theart, as seen by reference to U.S. Patent Publication 2009/0171343,application Ser No. 11/968,044 filed Dec. 31, 2007 entitled“PRESSURE-SENSITIVE FLEXIBLE POLYMER BIPOLAR ELECTRODE”, assigned to thecommon assignee of the present invention, and hereby incorporated byreference in its entirety.

FIG. 19 is flowchart of a method for optical-based tissue sensing toconfirm the progress of and successful completion of electroporationtherapy. The method begins in step 150.

In step 150, the electrochromic dyes 146, as described above, areapplied to the tissue 112, in any of the ways set forth above. Themethod proceeds to step 152.

In step 152, the control unit 124 generates the control signal Si toactivate the light source 120 to irradiate the tissue 112 withelectromagnetic radiation (light) 132. At the same time (i.e., at afirst time after the dye has been applied but before an electric fieldhas been applied to the tissue), the control unit 124 monitors (e.g.,samples) the signal S₂ generated by the light detector 122. The analyzer136 assesses the samples of the signal S₂, which is indicative of thelight 134 picked up at the distal end of the optic fiber 118, toestablish a first, baseline optical characteristic (step 154) of theelectrochromic dye at the tissue site 112. It should be appreciated thatthe return light signal 134 is dye-mediated. In one embodiment, theoptical characteristic(s) assessed include a light intensity and aspectral assessment (i.e., color) of the light signal 134 acquired attissue 112. In other words, the analyzer 138 measures and records thebaseline light intensity and optionally color or other spectralsignature (see block 140 in FIG. 18). The analyzer 138 will use thisbaseline optical characteristic stored in block 140 to make subsequentassessments.

In step 156, the electroporation system 148 is operative to energize theelectroporation electrodes (not shown in FIG. 18) in accordance with anelectroporation energizing strategy to establish an electric field inthe vicinity of the tissue 112. The method proceeds to step 158.

In step 158, the analyzer 138 continues to monitor the signal S2 outputfrom the sensor 122, which as described above corresponds to the lightsignal 134 acquired at the tissue site 112. As described in theBackground, an obstacle to the use of electroporation therapy forcertain therapeutic applications involves the time lag in confirming thesuccess of the therapy. In accordance with the invention, the analyzer138 is configured to continue to monitor the signal S2 while theelectric field is being applied even after the baseline opticalcharacteristic has been set. During application of the electric field astypically used to effect electroporation, the electrochromic dye willexhibit an “optical radiation storm” of intense color change. This isbecause the subject dyes change emission proportional to the voltageacross them, which in this case is the cell depolarization voltage sincethe dyes bind to the membrane. Embodiments of the invention may use this“optical radiation storm” as an indicator/monitor of the in situstrength of the electric field on the cell membrane during theelectroporation therapy. Accordingly, the analyzer 138 is configured tomonitor the optical detector output signal S2 looking for an opticalcharacteristic representative of an “optical radiation storm”. In anembodiment, the analyzer 138 is configured to detect a color change(e.g., through spectral/wavelength analysis), and more specifically, ina preferred embodiment, a color change compared to the baseline (i.e.,with the cells at rest). It should be further understood that the once aparticular dye has been selected, its color shift (e.g., to red orviolet) will be known and thus can be anticipated by the analyzer logic38 (i.e., can be configured to look specifically for a spectralcomponent). It should be further understood that while the dye itselfexhibits a color shift, perhaps to a particular part of the spectrum insome embodiments, that the dye color may be distinct from the displaycolor used to represent the tissue to the physician (i.e., on a displayscreen). In this regard, while information indicative of the dye colormay be captured using a light-to-voltage converter, the color or mode ofthe display of this information is independent. This is shown in step160 (i.e., see step 160—detection of the “optical radiation storm”).

In one embodiment, the “optical radiation storm” is detected based on achange in color of the light 134 (as represented by signal S₂) relativeto the color of the baseline optical characteristic recorded before theelectric field was applied. In another embodiment, the color of theoptical radiation storm is known ahead of time, and the analyzer 138 maybe configured to detect such a condition, even without comparison to thecolor/spectrum of the baseline reading.

The analyzer 138 is further configured to output a suitable indication(see block 142 in FIG. 18) when it detects the “optical radiation storm”(i.e., indicative of adequate electric field strength forelectroporation on the cell membrane). The method proceeds to step 162,where the electroporation system 148 de-energizes the electroporationelectrodes (not shown) that were used to create the electric field,thereby discontinuing the electric field. The method proceeds to step164.

Alternately, however, in FIG. 19, the step (or block) 164 may be aboveor in other words precede step (or block) 162. This ordering may be usedbecause typically the method may dictate that the electric field bestopped after, or in response to, the detection of the “Optical BlackOut.” (block 166).

In step 164, the analyzer 138 continues to monitor the optical detectoroutput signal S2. An efficacious electroporation is expected to causethe electrochromic dyes to be removed from the surface of the cellmembrane, thereby resulting in a “black out” of the dye-mediated opticalsignal from the target tissue 112 (i.e., the light signal 134). This“black out” may be used by the system 110 (analyzer 138 in particular)as a confirmation of the efficacy of electroporation in the targettissue 112. Accordingly, the analyzer 138 in step 164 is configured tocontinue to monitor signal S2 for an “optical black out” (step 166). Inan embodiment, the analyzer 138 is configured to assess the lightintensity level represented in the monitored signal S₂ relative to thelight intensity level represented in the baseline opticalcharacteristic. When the light intensity level has been reduced by atleast a predetermined amount (i.e., “black out”), then the analyzer 138produces an output indication (see block 142 FIG. 18), which may includea confirmation of the efficacy of the electroporation therapy.

FIGS. 20-21 show fiber optic temperature sensing electrode systems infirst and second embodiments. Generally, temperature sensing is achievedby using thermochromic or thermotropic materials, such as a temperaturesensitive dye, polymers or hydrogels, that change color in response tochanges in temperature. For example, a thermochromic solution ofCoCl₂.6H₂0 may be used as a temperature sensing material. The use of thethese materials overcomes the problems described in the Backgroundpertaining to temperature sensing errors due to location eccentricity ofthermocouples or thermistors.

FIG. 20 is a combined partial cross-sectional and block diagram of afiber optic temperature sensing electrode system 170 comprising aplurality of proximal-side components collectively designated 172 and anelectrode catheter in a first embodiment designated 174 a. A first lightsignal transmitted to the electrode catheter 174 a and a second lightsignal returning to the proximal-side components are shown in acomposite manner by the double arrow-headed line 176.

The electrode catheter 174 a includes a shaft 178 having a proximal end180 and a distal end 182. The shaft 178 may be of conventionalconstruction and materials, such as that described above in connectionwith FIG. 18.

The catheter 174 a further includes an electrode 184 at the distal end182. The electrode 184 includes a main body portion having an outersurface 186 and an inner cavity 188 defined by an inner surface 190. Theelectrode 184 may comprise conventional electrically-conductivematerials, such as described above in connection with FIGS. 2-4 forexample. It should understood, however, that other electrodeconstruction approaches and materials may be used. For example, theelectrode 184 may alternatively comprise an electrically-conductiveelectrode configured for use in irrigated-electrode application, aflexible polymer electrode or a fiber optic electrode.

At least a portion of the inner surface 190 comprises athermally-sensitive material 192 configured to change color as afunction of temperature, such as thermochromic or thermotropicmaterials. In FIG. 20, the material 192 is shown as a series of “o”symbols distributed along the inner surface 190. In one embodiment, thematerial 192 may be impregnated into the inner surface of the electrode184. In an alternate embodiment, the material 192 may be applied as athin coating to the inner surface 192 of the electrode 184.

FIG. 21 shows another embodiment of the catheter for use in system 170,designated electrode catheter 174 b. The catheter 174 b differs withrespect to the catheter 174 a of FIG. 20 in that the optic fiberincludes a lumen at its distal end that is at least partially filledwith the material 192, rather than the material 192 being eitherimpregnated or applied as a thin layer as in FIG. 21. The system 170 ofFIG. 21 may otherwise in all respects be the same as the system of FIG.20.

The catheter 174 a further includes at least one optic fiber 194 in theshaft 178 extending between the proximal and distal ends 180, 182. Theoptic fiber 194 includes proximal and distal ends 196, 198 as well. Thedistal end 198 of the optic fiber 194 is in optical communication withthe material 192 (e.g., in optical communication with the cavity, theinner surface thereof or a lumen having or containing the material 192as in FIG. 21). In this regard, the optic fiber 194 may have its distalend 198 finished or otherwise provided with a lens or other structure tofacilitate acquisition of a light signal in accordance with conventionalapproaches. The optic fiber 194 may be of conventional construction andmaterials, such as for example as described above in connection withFIG. 18.

The proximal-side components 172 include a light source 200, an opticaldetector 202 generating an output signal 204, a control unit 206 (e.g.,an electronic control unit (ECU)) having an analyzer portion 208, astorage mechanism 210 for storing predeterminedspectrum-versus-temperature calibration data and an output block 212,which may comprise a temperature signal indicative of a temperature ofthe electrode 184.

The light source 200 is configured to generate a first light signal. Theproximal end 196 of the optic fiber 194 is configured to interface withthe light source 200 and carry the first light signal to its distal end198, where the first light signal is projected onto and is incident uponat least the thermally-sensitive material 192. The distal end 198 of theoptic fiber 194 is further configured to acquire a second light signalthat is reflected, refracted or is otherwise available within the cavity188. The optic fiber 194 is further configured to transmit the secondlight signal acquired at its distal end 198 to its proximal end 196. Theoptical detector 202 is optically coupled to the distal end 198 and isconfigured to detect the second light signal and generate the outputsignal 204. The light source 200 and the optical detector 202 maycomprise conventional components, such as those described above inconnection with FIG. 18.

The analyzer 208 of the control unit 206 is configured to assess thedetector output signal 204 and generate a temperature signal 212representative of the temperature of the electrode 184. In anembodiment, the analyzer 208 is configured to use predeterminedcalibration data 210, which may comprise data that correlates thespectrum (i.e., a wavelength-intensity curve) of the received light asrepresented by output signal 204 with a corresponding temperature. Itshould be understood that the calibration data 210 will be tailored tosuit the characteristics of the material 192, with the foregoing beingexemplary only and not limiting in nature. The control unit 206 maycomprise conventional components, as described above in connection withFIG. 18, subject to being specially-configured by way of analyzer 208 toperform the functions described herein. In sum, the thermochromicmaterial serves as a temperature-to-light converter while the opticaldetector serves as the light-to-voltage converter. The analyzer 208evaluates the voltage signal 204 based on the conversion relationshipsdetermined to faithfully take into account the temperature-to-light andlight-to-voltage conversion processes to produce an indication of sensedtemperature. The calibration data 210 may be used to adjust theconversion relationships to any variations in the temperature-to-lightand light-to-voltage conversion processes. In an embodiment, thecalibration data 210 may updated from time to time to take into accountchanges in the temperature-to-light and light-to-voltage conversionprocesses that may occur over time.

Through the foregoing, temperature sensing errors may be avoided. Inaddition, the optic fiber is immune to radiofrequency interference (RFI)and electromagnetic interference (EMI), and accordingly embodimentsconsistent with the invention may likewise exhibit such immunity.

The embodiments described herein enable a variety of applications ofelectroporation therapy, including the ability (1) to modulate tissueproperties, such as (i) electrical conductivity of the tissue in orderto make the tissue more responsive/irresponsive to RF ablation, and/or(ii) chemical/electrochemical properties of the tissue in order to makethe tissue more responsive/irresponsive to photodynamic based tissuesensing and/or ablation, and/or (iii) acoustic properties of the tissuein order to make the tissue responsive/irresponsive to ultrasound basedtissue sensing and/or ablation; and/or (2) to confirm the target tissue(such as an ectopic site); and/or (3) to prevent stenosis.

It should be understood that the various control units, computer systemsand the like described herein may include conventional processingapparatus known in the art (i.e., both hardware and/or software),including the capability of executing pre-programmed instructions storedin an associated memory, all performing in accordance with thefunctionality described herein. It is contemplated that the methodsdescribed herein, including without limitation the method steps ofembodiments of the invention, may be programmed in a preferredembodiment, with the resulting software being stored in an associatedmemory and may also constitute the means for performing such methods.Implementation of embodiments, in software, in view of the foregoingenabling description, would require no more than routine application ofprogramming skills by one of ordinary skill in the art. The system mayfurther be of the type having both ROM, RAM, a combination ofnon-volatile and volatile (modifiable) memory so that the software canbe stored and yet allow storage and processing of dynamically produceddata and/or signals. Moreover, an article of manufacture in accordancewith embodiments of the invention includes a computer-readable storagemedium having a computer program encoded thereon for performing themethods described in this application. The computer program includescode that, when executed by a computer, causes the computer to performthe steps of the methods described herein.

Although numerous embodiments of this invention have been describedabove with a certain degree of particularity, those skilled in the artcould make numerous alterations to the disclosed embodiments withoutdeparting from the spirit or scope of this invention. All directionalreferences (e.g., plus, minus, upper, lower, upward, downward, left,right, leftward, rightward, top, bottom, above, below, vertical,horizontal, clockwise, and counterclockwise) are only used foridentification purposes to aid the reader's understanding of the presentinvention, and do not create limitations, particularly as to theposition, orientation, or use of the invention. Joinder references(e.g., attached, coupled, connected, and the like) are to be construedbroadly and may include intermediate members between a connection ofelements and relative movement between elements. As such, joinderreferences do not necessarily infer that two elements are directlyconnected and in fixed relation to each other. It is intended that allmatter contained in the above description or shown in the accompanyingdrawings shall be interpreted as illustrative only and not limiting.Changes in detail or structure may be made without departing from thespirit of the invention as defined in the appended claims.

1.-20. (canceled)
 21. An electroporation therapy system, comprising: adevice having proximal and distal ends; an electrode assembly comprisinga plurality of electrically isolated ring electrode elements disposed atsaid distal end of said device, wherein said plurality of electrodeelements are disposed on an outer surface of a base wherein said basecomprises electrically-insulating material, said base having an arcuateshape; and an electroporation generator coupled to said electrodeelements and configured to energize said one or more of said electrodeelements in accordance with an electroporation energization strategy,said electroporation generator being configured to selectively energizesaid one or more electrode elements in a bipolar fashion so as toproduce a lesion in said tissue.
 22. The system of claim 21 wherein saidbase having said arcuate shape comprises one of (i) a materialcomposition and structure so as to be flexible to allow bending intosaid arcuate shape; (ii) a mechanism to impart said arcuate shape tosaid base; and (iii) is preformed to have said arcuate shape.
 23. Thesystem of claim 21 wherein said base has a straight portion having anaxis and a distal portion having said arcuate shape.
 24. The system ofclaim 21 wherein said base is configured as a loop.
 25. The system ofclaim 21 wherein said base comprises a tubular base.
 26. The system ofclaim 21 wherein said arcuate shaped base may be shaped relative to ashaft of said device such that the shaft and base together take anoverall shape of a hockey stick, a question mark, or a spiral.
 27. Thesystem of claim 21 wherein adjacent electrode elements define bi-polesfor said bipolar fashion energization.
 28. The system of claim 21wherein said electroporation generator is configured to produce anelectric current that is delivered via said electrodes as a pulsedelectric field.
 29. The system of claim 28 wherein said electroporationenergizing strategy includes a pulse magnitude, number, and duration.30. The system of claim 28 wherein said electroporation energizingstrategy is chosen based on a therapy selected from the group comprisingan electroporation-induced primary necrosis therapy and an electricfield-induced apoptosis therapy.
 31. The system of claim 30 wherein saidselected therapy is said electroporation-induced primary necrosistherapy, and wherein said electroporation generator is configured toproduce said electric current as said pulsed electric field in the formof short-duration direct current (DC) pulses having a relatively lowelectric field strength.
 32. The system of claim 31 wherein saidelectric field strength is between about 0.1 and 1.0 kV/cm.
 33. Thesystem of claim 30 wherein said selected therapy is said electricfield-induced apoptosis therapy, and wherein said electroporationgenerator is configured to produce said electric current as said pulsedelectric field in the form of short-duration direct current (DC) pulseshaving a relatively high electric field strength.
 34. The system ofclaim 33 wherein said electric field strength is between about 2 and 300kV/cm.
 35. The electroporation therapy system of claim 21 furthercomprising: a detector coupled to said plurality of electrode elementsconfigured to identify which of said plurality of ring electrodeelements have a conduction characteristic indicative of contact withtissue; and a tissue sensing circuit coupled to said detector whereinsaid tissue sensing circuit is configured to determine, for eachelectrode element, a respective electrical characteristic associatedwith each electrode element to determine whether each electrode elementis in contact with tissue, wherein said electroporation generator iscoupled to said detector, and wherein said generator is furtherconfigured to energize said identified electrode elements.
 36. Thesystem of claim 35 wherein said tissue sensing circuit includes a tissuesensing signal source for generating an excitation signal used fordetermining said electrical characteristic, said detector beingconfigured to receive said electrical characteristic from said tissuesensing circuit and to determine which of said electrode elements is intissue contact based on a respective value of said electricalcharacteristic and predetermined threshold data.
 37. The system of claim35 wherein said electroporation generator is configured to energize saididentified electrode elements that are less in number than saidplurality of electrically isolated electrode elements and to notenergize electrode elements that are not identified by said detector ashaving a conduction characteristic indicative of contact with tissue.38. The system of claim 35 wherein said electrical characteristiccomprises one of an impedance, a phase angle, a reactance, and anelectrical coupling index.
 39. The system of claim 21 wherein saidelectrode elements are substantially evenly spaced on said base.
 40. Thesystem of claim 21 wherein said electrode elements are substantiallyflush with said outer surface of said base.